Original Title: Arzneimittel-Richtlinie/Anlage XII: Asciminib (Chronische myeloische Leukämie, Ph+, nach ≥ 2 Vortherapien)

Authors' objectives: The Federal Joint Committee [Gemeinsamer Bundesausschuss (G-BA)] has had the legal task of carrying out an (additional) benefit assessment for all newly approved drugs with new active ingredients immediately after market entry (§ 35a SGB V). The result of this assessment is the basis for deciding how much the statutory health insurance pays for a new drug with a new active ingredient. The G-BA was commissioned to carry out the benefit assessment through the Pharmaceuticals Market Reorganisation Act [Gesetz zur Neuordnung des Arzneimittelmarktes (AMNOG)]. In the context of the early benefit assessment of medicinal products containing new active substances, the following rules apply to orphan drugs: According to the legal requirements (§ 35a SGB V), the additional medical benefit of these drugs is already considered to be proven by the approval. The G-BA determines the extent of the additional benefit for orphan drugs that do not exceed a turnover of 50 million Euros in the last twelve calendar months, on the basis of the approval and the studies justifying the approval.

Authors' results and conclusions: Asciminib is approved for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (Ph+ CML-CP) previously treated with ≥2 tyrosine kinase inhibitors. The benefit assessment report was based on the pivotal trial ASCEMBL (CABL001A2301), a phase 3, multi-center, open-label, randomized study of asciminib (N=157) versus bosutinib (N=76) in the targeted CML-Ph+-population. Results were available for interims cut-off date of 06-Oct-2021. A treatment switch was allowed in the control arm to asciminib if patients meeting protocol defined lack of efficacy criteria (n=24 in control arm). Risk of bias was considered high due to open study design. Results for overall survival and progression to blast crisis were comparable with low number of events in both treatment arm. At week 24, statistically significant difference in favor of asciminib was shown for major molecular response rate (RR: 1.93; 95% CI: 1.03; 3.62]; p-value: 0.029). However, the endpoint was not considered as a patient-relevant endpoint. Symptom burden and interference according to MDASI-CML showed a statistically significant but not clinically relevant difference in favor of asciminib (LS means difference: -0.5 (95% CI: -0.9; 0.1); p-value: 0.007). Uncertainties in interpreting efficacy results remain regarding single-arm switch of patients in the control arm to asciminib and shorter observation time in comparison to study duration and observation time differences between treatment arms. Frequency of adverse events (AE) was less for asciminib treated patients compared to bosutinib which was statistically significant in favor of asciminib for severe or serious AE, respectively (p-value <0.05) or AE leading to study drug discontinuation (p-value: <0.001). For the later endpoint, uncertainties in interpreting the results remain due to competing risks (e.g. reasons for discontinuation other than AEs and differences in observation time between study arms).

Project Status: Completed

URL for project: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/884/#english

Year Published: 2023

URL for published report: https://www.g-ba.de/downloads/39-1464-5906/2023-03-16_AM-RL-XII_Asciminib_D-865_EN.pdf

Requestor: The Federal Joint Committee [Gemeinsamer Bundesausschuss] (G-BA)

URL for additional information: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/884/#nutzenbewertung

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Germany

Organisation Name: The Federal Joint Committee

Contact Address: Gutenbergstr. 13, 10587 Berlin, Germany

Contact Name: Fachberatung Medizin [Department of Medical Consultancy]

Contact Email: Fachberatung-Medizin@g-ba.de

Copyright: https://www.g-ba.de/sys/impressum/